Introduction

At present we are in an era of controlled clinical trials evaluating chemoendocrine agents in the prevention of breast cancer. Although breast cancer deaths (in the UK and USA) have now started to decline (Peto et al., 2000), the commitment to this approach originated in the recognition that early diagnosis and improvements in treatment had not translated into an order of magnitude step-down in mortality figures. Research directed at primary prevention of breast cancer has become a priority, especially for those women who are at increased risk of developing the disease. This is further enhanced by the emerging detail of breast cancer genetics, heralded with the identification of BRCA1 and BRCA2, and the consequent ability to refine risk assessment, along with developments in the understanding of breast cancer biology, the oestrogen receptor (ER) and the availability of new selective oestrogen receptor modulators (SERMs).

In the early months of the year 2000 there was intense pressure on these prevention trials. Tamoxifen in the National Surgical Adjuvant Breast and Bowel Project (NSABP) P1 Breast Cancer Prevention Trial has been reported to reduce the incidence of invasive (and noninvasive) breast cancer when compared to placebo (Fisher et al., 1998), and as a consequence the Food and Drug Administration (FDA) have approved tamoxifen for breast cancer risk reduction in high-risk women. In contradistinction, the preliminary analyses of the Royal Marsden, London, UK and Italian tamoxifen randomized chemoprevention trials (Powles et al., 1998a; Veronesi et al., 1998) yielded null results.